Immunity is normally exhausted in people who have chronic hepatitis
C. Alternative forms of two genes are associated with a boost in
immunity to hepatitis C after childbirth, suggested a study led by a Nationwide
Children's Hospital physician-researcher.
At three months postpartum, the number of viruses circulating in the
blood declined sharply in most women who carried particular versions of
IFNL3 and HLA-DPB1 genes. Mothers lacking these gene variants
experienced little change in viral levels after delivery.
‘Alternative forms of two genes are associated with a boost in immunity to hepatitis C after childbirth. The findings may provide a model for identifying immune factors needed to control chronic infections.’
The research is published in the Proceedings of the National Academy of Sciences
The study focused on hepatitis C, but it may serve as a model for
identifying factors that restore immunity to other chronic infections,
the researchers suggest.
"In chronic hepatitis C the liver produces about a trillion viruses per day, and the
T-cells that should attack the virus don't work," says Jonathan R. Honegger, principal investigator at the Center for Vaccines and Immunity in The Research Institute at Nationwide Children's, and lead study author.
While studying hepatitis C transmission from mother to baby, he
noticed that some mothers experienced unusual sharp declines (10-1000
fold) in blood viral levels after childbirth. Women with these viral
load declines also had improved T-cell activity against hepatitis C
"These initial observations really piqued our interest. There's a
lot of effort underway to find ways to turn on exhausted T-cells, and
the months following pregnancy appeared to provide a unique opportunity
to study this," says Dr. Honegger, who is also assistant professor of
clinical pediatrics at The Ohio State University College of Medicine.
Among 34 women in this study, five had consecutive pregnancies. "The
postpartum viral load decline was very similar with each consecutive
pregnancy, which made you think it wasn't just a random event - that some
stable factor was controlling how viremia fell after delivery," Dr.
The team focused on genes.
Interferon lambda 3, a signaling protein that induces antiviral
activity, is known to affect control hepatitis C in non-pregnant people.
The researchers found that a common variant in the IFNL3 gene also
increases the likelihood of controlling hepatitis C after pregnancy.
Human leukocyte antigen (HLA) molecules present small pieces of
proteins to T-cells, enabling T-cells to recognize the presence of
foreign pathogens such as viruses. The team found that women who
possessed particular variants of HLA-DBP1 genes demonstrated greater
T-cell recovery and virus control than women lacking these variants.
HLA-DPB1 molecules present peptides to a type of T-cell called CD4+
"helper" T-cells. "This finding was important because helper T-cells
are thought to be particularly dysfunctional in chronic hepatitis C.
These findings suggest that HCV-specific helper T-cells may regain
function after delivery. This is now an active line of investigation
Reversal of T-cell exhaustion may also be relevant for controlling
other persistent infections such as hepatitis B or HIV, the researchers
In another study to be published, the researchers examined
effects of the IFNL3 genotype on immune gene signaling after childbirth
in un-infected women.